GRAIN Study - Granulocytes Against Infections - Use of granulocyte transfusion in haematopoietic stem cell transplant.

Granulocyte transfusions (GTx) combat infections in neutropenic patients. However, immune-mediated off-target effects in transplant settings are unknown. Between January 2020 and December 2021, all transplants that used GTx during the peri-transplant period were analysed. Engraftment, infections, and days to clearance were retrieved from clinical records. Overall survival is compared with the mean total PMN count and the different products. Pooled buffy coat was used in 110 patients (98 %), of which 38 (34 %) additionally received an apheresed product. The median days of GTx was 4. The median bags pooled to prepare a single buffy coat product was 4. The mean total PMN count was 0.98 × 1010/ L granulocytes per pooled buffy coat and 1.93 × 1010/L granulocytes per apheresis product. A higher PMN count (>1 × 1010/L) was achieved in 48 % with pooled buffy coat versus 85 % with apheresis. Respiratory worsening occurred in 39 % receiving GTx. All patients who received granulocytes had engrafted with a median time of 14 days for neutrophil and 20 days for platelet engraftment. Blood cultures cleared in 81 %, whereas only 28 % cleared other cultures. Fungal pneumonia cleared in 25 %, and invasive fungal sinusitis or otitis cleared in 50 %. Overall survival was 47 %, non-significantly higher (57 % vs 39 %, P = 0.1) with a higher PMN dose. The pooled buffy coat is an affordable alternative to apheresis for an effective PMN dose. Ease of availability and low cost of pooled buffy coat, with comparable overall survival points toward a safe and efficacious product, in the peri-transplant period.

Total Marrow and Lymphoid Irradiation [TMLI] is associated with good early outcomes in patients undergoing matched sibling donor and haplo-identical transplants for acute lymphoblastic leukemia.

INTRODUCTION: Total marrow and lymphoid irradiation [TMLI] can deliver higher doses of irradiation without increased toxicity. This study evaluated TMLI and Cyclophosphamide in patients undergoing stem cell transplantation for acute lymphoblastic leukemia [ALL] . METHODS: Fifty-eight patients underwent matched related, unrelated or haplo-identical donor transplant using TMLI. The graft source was PBSC in all while GVHD prophylaxis consisted of cyclosporine with methotrexate or post-transplant cyclophosphamide. RESULTS: The median age was 20 years [range: 5 - 49] and included 20 children. Engraftment occurred in 56 [96.5%] at median of 15 days [range: 12 - 23] with 2 early deaths. Sinusoidal obstruction syndrome [SOS] was seen in 10 patients while hemorrhagic cystitis and cardiac dysfunction occurred in 2 patients each. Cumulative incidence of grade II - IV acute GVHD was 23.6% while grade III - IV was 10.9%. Chronic GVHD was seen in 46.9% while relapse was seen in 10 patients [17.2%]. The 2-year overall survival [OS] was 65.9 ± 6.8% and 2-year disease free survival [DFS] was 59 ± 6.7%. Outcomes were compared with 52 patients who received either Cy/TBI or Flu/Bu4 for conditioning during the same period. Engraftment rates and time to engraftment were similar. Acute GVHD [p = 0.002], regimen related toxicity [p = 0.043] and Day 100 non-relapse mortality [p = 0.020] were significantly lower with TMLI. TMLI was associated with better OS [p = 0.004] and DFS [p = 0.005] for haplo-identical transplants. Better DFS was seen with TMLI in patients with high-risk disease [p = 0.007] and disease status > CR1 [p = 0.041]. CONCLUSION: The use of TMLI and cyclophosphamide is associated with good outcomes in patients undergoing HSCT for ALL especially with haploidentical stem cell transplants.

Fungal Intracranial Infections (Central Nervous System-Invasive Fungal Disease) in Patients With Haematological Disorders-A Single-Centre Retrospective Study.

BACKGROUND: Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes. OBJECTIVES: To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder. PATIENTS AND METHODS: This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022. RESULTS: Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46). CONCLUSION: CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy.

Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome - evaluation of a large cohort in India.

BACKGROUND: The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available. METHODS: We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC). RESULTS: There were 936 patients aged 18-86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1-3% each. CONCLUSION: The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS.

Impact of the COVID-19 pandemic on treatment of patients with acute myeloid leukaemia in India.

During the COVID-19 pandemic, our findings highlight changes in AML management strategies in India. There was a decrease in overall patient registrations, particularly at large referral centers, while smaller centers saw an increase, reflecting a shift towards more localized care. This shift was accompanied by a rise in the use of hypomethylating agents (HMAs). Despite these changes, survival outcomes remained comparable to pre-pandemic levels, likely due to improved infection control measures and maintaining treatment protocols. Our study concludes that standard AML care remained feasible during the pandemic, emphasizing the importance of continuing treatment for eligible patients even in times of crisis.

Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study.

Background: Patient-reported outcomes (PROs) reflect patient perceptions of disease and treatment and are important for evaluating new therapies. Objectives: Evaluate the effects of once-daily concizumab prophylaxis on health-related quality of life (HRQoL), treatment burden, and treatment preference in males aged ≥12 years with hemophilia A/B with inhibitors. Methods: Patients enrolled in the multicenter, open-label explorer7 phase 3 study (ClinicalTrials.gov identifier: NCT04083781) were randomized to receive no prophylaxis (arm 1) or concizumab prophylaxis (arm 2) or were nonrandomly allocated to concizumab prophylaxis (arms 3 and 4). The study included questionnaires to assess patients' perception of HRQoL (Haemophilia Quality of Life Questionnaire for Adults), treatment burden (Hemophilia Treatment Experience Measure), and treatment preference (Haemophilia Patient Preference Questionnaire). Results: The estimated treatment difference between patients receiving concizumab prophylaxis vs no prophylaxis at week 24 for Haemophilia Quality of Life Questionnaire for Adults "total score" was -22.6 points (95% CI, -42.5; -2.7), directionally favoring patients receiving concizumab prophylaxis. For Hemophilia Treatment Experience Measure "total score," the estimated treatment difference was -19.9 points (95% CI, -34.3, -5.6) in favor of concizumab vs no prophylaxis. The majority of patients receiving concizumab expressed a preference for concizumab over their previous treatment, the main reasons being "fewer bleeds," "require less time," and "less painful to inject." Across all PROs, there were less responses collected than anticipated, limiting interpretations. Conclusion: PROs collected during the explorer7 study showed improvements in some domains of HRQoL, treatment burden, and patient treatment preference in persons with hemophilia A or B with inhibitors receiving concizumab prophylaxis compared with no prophylaxis.

Improving Outcomes with Haploidentical Stem Cell Transplantation [HaploSCT] in Children Using Post-transplant Cyclophosphamide: a Single Center Experience.

Haplo-identical stem cell transplant using post-transplant cyclophosphamide is increasingly being used in children without a matched sibling donor. Between 2010 and June 2021, 127 children underwent 138 transplants with a median age of 7.1 years for malignant and non-malignant disorders. Conditioning regimens included both myeloablative and reduced intensity regimens with peripheral blood stem cells as the main graft source. Engraftment occurred in 113 [81.9%] at a median of 16 days [range: 10-32] with primary graft failure in 10.2%. Cumulative incidence of grade II-IV acute graft versus host disease (GVHD) was 49.5% and chronic GVHD in 40.7%. Majority [92.7%] had at least one infection with 31% incidence of bacterial infection, 76% incidence of viral and 16% incidence of fungal infection. The 2-year overall survival (OS) is 54.9 ± 4.6% with a lower survival among young children aged 0-5 years [28.2 ± 6.4%] compared to 5-10 years [71.3 ± 6.8%] and 11-15 years [55.7 ± 8.8%] [p = 0.032]. 2-year OS has gradually improved from 25.0 ± 2.1% for 2010-2013 to 47.5 ± 6.2% for 2014-2017 and 67.1 ± 6.6% for 2018-2021 [p = 0.049]. On multivariate analysis, bacterial infection [p = 0.017], invasive fungal disease [p = 0.002] and graft failure [p = 0.029] negatively impacted overall survival. Haplo-identical SCT with post-transplant cyclophosphamide is a reasonable option for children who do not have a matched sibling donor. Strategies to reduce graft failure, infection related mortality and GVHD needs to be explored.

Treatment challenges and outcomes of older patients with acute myeloid leukemia from India.

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

Ablation of Wnt signaling in bone marrow stromal cells overcomes microenvironment-mediated drug resistance in acute myeloid leukemia.

The survival of leukemic cells is significantly influenced by the bone marrow microenvironment, where stromal cells play a crucial role. While there has been substantial progress in understanding the mechanisms and pathways involved in this crosstalk, limited data exist regarding the impact of leukemic cells on bone marrow stromal cells and their potential role in drug resistance. In this study, we identify that leukemic cells prime bone marrow stromal cells towards osteoblast lineage and promote drug resistance. This biased differentiation of stroma is accompanied by dysregulation of the canonical Wnt signaling pathway. Inhibition of Wnt signaling in stroma reversed the drug resistance in leukemic cells, which was further validated in leukemic mice models. This study evaluates the critical role of leukemic cells in establishing a drug-resistant niche by influencing the bone marrow stromal cells. Additionally, it highlights the potential of targeting Wnt signaling in the stroma by repurposing an anthelmintic drug to overcome the microenvironment-mediated drug resistance.

Relapse and transformation to myelodysplastic syndrome and acute myeloid leukemia following immunosuppressive therapy for aplastic anemia is more common as compared to allogeneic stem cell transplantation with a negative impact on survival.

We studied the incidence of relapse, transformation to myelodysplastic syndrome/acute myeloid leukemia, and survival in patients with aplastic anemia (AA) surviving more than 1 year after ATG/ALG-based immunosuppressive therapy (IST) between 1985 and 2020. Four-hundred seventy patients (413 adults and 57 children) were studied, and data were compared with 223 patients who underwent matched sibling donor transplant (MSD HSCT). Median follow-up is 50 months (12-359). Relapse occurred in 21.9% at a median time of 33.5 months (5-228) post IST. Twenty-six (5.5%) patients progressed to PNH, while 20 (4.3%) evolved to MDS/AML. Ten-year estimated overall survival (OS) is 80.9 ± 3% and was significantly better in patients without an event (85.1 ± 4%) compared to relapse (74.6% ± 6.2%) or clonal evolution (12.8% ± 11.8%) (p = 0.024). While the severity of AA (p = 0.011) and type of ATG (p = 0.028) used predicted relapse, only age at IST administration influenced clonal evolution (p = 0.018). Among HSCT recipients, relapse rates were 4.9% with no clonal evolution, and the 10-year OS was 94.5 ± 2%. In patients who survived 1 year following IST, outcomes were good except with clonal evolution to MDS/AML. These outcomes, however, were still inferior compared to matched sibling donor HSCT.

Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

INTRODUCTION: Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. PATIENTS AND METHODS: The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. RESULTS: Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90 degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. CONCLUSION: This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Comparison of telomere length in patients with bone marrow failure syndromes and healthy controls.

INTRODUCTION: During normal aging, telomeric DNA is gradually lost in dividing somatic cells, and critically short telomeres lead to replicative senescence, apoptosis, or chromosomal instability. We studied telomere length in bone marrow failure syndromes (BMFS) compared to normal healthy population. METHODS: Peripheral blood was collected from the participants, and genomic DNA was extracted. Relative telomere length was measured using a quantitative polymerase chain reaction. Statistical analysis was performed using SPSS and GraphPad Prism 8.2 software. RESULTS: The median age of normal Indian population was 31 (0-60) years. As expected, telomere length (TL) showed a decline with age and no difference in TL between males and females. The median age of 650 patients with aplastic anemia (AA) was 30 (1-60) years. TL was significantly shorter in patients with AA compared to healthy controls (p < .001). In FA and MDS patients, TL was significantly shorter than age-matched healthy controls (p = .028; p < .001), respectively. There was no difference between the median TL in age-matched AA and FA patients (p = .727). However, patients with MDS had shorter TL than age-matched AA (p = .031). CONCLUSION: TL in BMF syndrome patients was significantly shorter than age-matched healthy controls.

Immortalised chronic myeloid leukemia (CML) derived mesenchymal stromal cells (MSCs) line retains the immunomodulatory and chemoprotective properties of CML patient-derived MSCs.

Despite the success of Tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML), leukemic stem cells (LSCs) persist, contributing to relapse and resistance. CML Mesenchymal Stromal Cells (MSCs) help in LSC maintenance and protection from TKIs. However, the limited passage and self-differentiation abilities of primary CML MSCs hinder extensive research. To overcome this, we generated and characterized an immortalised CML patient-derived MSC (iCML MSC) line and assessed its role in LSC maintenance. We also compared the immunophenotype and differentiation potential between primary CML MSCs at diagnosis, post-treatment, and with normal bone marrow MSCs. Notably, CML MSCs exhibited enhanced chondrogenic differentiation potential compared to normal MSCs. The iCML MSC line retained the trilineage differentiation potential and was genetically stable, enabling long-term investigations. Functional studies demonstrated that iCML MSCs protected CML CD34+ cells from imatinib-induced apoptosis, recapitulating the bone marrow microenvironment-mediated resistance observed in patients. iCML MSC-conditioned media enabled CML CD34+ and AML blast cells to proliferate rapidly, with no impact on healthy donor CD34+ cells. Gene expression profiling revealed dysregulated genes associated with calcium metabolism in CML CD34+ cells cocultured with iCML MSCs, providing insights into potential therapeutic targets. Further, cytokine profiling revealed that the primary CML MSC lines abundantly secreted 25 cytokines involved in immune regulation, supporting the hypothesis that CML MSCs create an immune modulatory microenvironment that promotes growth and protects against TKIs. Our study establishes the utility of iCML MSCs as a valuable model to investigate leukemic-stromal interactions and study candidate genes involved in mediating TKI resistance in CML LSCs.

Treosulfan Exposure Predicts Thalassemia-Free Survival in Patients with Beta Thalassemia Major Undergoing Allogeneic Hematopoietic Cell Transplantation.

A toxicity-reduced conditioning regimen with treosulfan, fludarabine, and thiotepa in patients with high-risk ß-thalassemia major has significantly improved hematopoietic stem cell transplantation (HCT) outcomes. However, complications resulting from regimen-related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose-exposure-response relationship of treosulfan and its active metabolite S, S-EBDM, in a uniform cohort of patients with ß-thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of treosulfan is feasible. Plasma treosulfan/S, S-EBDM levels were measured in 77 patients using a validated liquid chromatography with tandem mass spectrometry method, and the pharmacokinetic parameters were estimated using nlmixr2. The influence of treosulfan and S, S-EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1-year overall survival (OS), and thalassemia-free survival (TFS) were assessed. We observed that treosulfan exposure was lower in patients with graft rejection than those without (1,655 vs. 2,037 mg•h/L, P = 0.07). Pharmacodynamic modeling analysis to identify therapeutic cutoff revealed that treosulfan exposure ≥1,660 mg•hour/L was significantly associated with better 1-year TFS (97% vs. 81%, P = 0.02) and a trend to better 1-year OS (90% vs. 69%, P = 0.07). Further, multivariate analysis adjusting for known pre-HCT risk factors also revealed treosulfan exposure <1,660 mg•h/L (hazard ratio (HR) = 3.23; 95% confidence interval (CI) = 1.12-9.34; P = 0.03) and GSTA1*B variant genotype (HR = 3.75; 95% CI = 1.04-13.47; P = 0.04) to be independent predictors for inferior 1-year TFS. We conclude that lower treosulfan exposure increases the risk of graft rejection and early transplant-related mortality affecting TFS. As no RRTs were observed with increasing treosulfan exposure, TDM-based dose adjustment could be feasible and beneficial.

Early detection, reactivation of cytomegalovirus DNA & immediate early (IE)-mRNA expression in hematopoietic stem cell-transplant patients.

BACKGROUND: Human cytomegalovirus (HCMV) reactivation is a major cause of morbidity and mortality among stem cell transplant recipients post-transplantation. AIM: HCMV immediate-early messenger RNA (IE-mRNA) was evaluated as marker of post-transplant HCMV reactivation in bone marrow transplant recipients. METHOD: ology: An in-house real-time reverse transcriptase PCR targeting IE-mRNA was developed to estimate HCMV mRNA levels post-transplantation. Blood samples collected in K2-EDTA tubes from patients (n = 162) admitted with Department of Clinical Hematology were transported in cold condition for routine HCMV DNA screening. For HCMV IE-mRNA quantification, peripheral blood mononuclear cells (PBMCs) were separated from whole blood and stored in RNA later at -70 °C until testing. Samples were collected weekly once for first 3 weeks post-transplantation and thereafter from week 4-12, samples were collected twice weekly. A total of 2467 samples were collected from 162 study participants. RESULTS: Thirty five patients (21.6 %) had post-transplant HCMV reactivation. Twenty five patients with complete follow-up were selected for monitoring HCMV DNA. HCMV IE-mRNA PCR was performed for 15 patients and 7(46.6 %) patients had detectable mRNA levels. HCMV IE-mRNA was detected in all patients with increasing HCMV DNA levels except for one patient in whom IE-mRNA appeared 3 days before HCMV DNA was detected. One patient had detectable HCMV IE-mRNA during declining HCMV DNA level. However the patient showed an increased HCMV DNA one week later, indicating the importance of HCMV mRNA in predicting HCMV replication. CONCLUSION: Quantification of HCMV IE-mRNA may be a valuable tool to predict progression of HCMV infection post-transplantation, with further prospective studies needed for validation.

Speckle tracking echocardiography-derived left ventricular global longitudinal strain in ex-thalassaemics.

AIMS: Long term survivors of haematopoietic stem cell transplantation (HSCT) for ß-thalassemia major are designated "ex-thalassaemics". Whether ex-thalassaemics continue to harbour residual myocardial dysfunction and thereby stand the risk of heart failure-related morbidity and mortality is unknown. The aim of this study was to assess the prevalence and predictors of subclinical left ventricular (LV) dysfunction in an apparently normal ex-thalassaemic population. METHODS: We conducted a single centre cross-sectional study among 62 ex-thalassaemic patients, who had undergone HSCT for ß-thalassaemia major at our centre. The primary outcome variable was LV systolic dysfunction, as assessed by 1) LV global longitudinal strain (GLS) derived by 2D speckle tracking echocardiography and 2) LV ejection fraction (EF) derived by 2D Simpsons Biplane method. RESULTS: Among the 62 patients included in the study, 7 [11.3%] were found to have LV systolic dysfunction, all of which were subclinical. Of these, 4 [6.5%] had abnormal GLS and LVEF, 2 [3.2%] had abnormal GLS with normal LVEF, and 1 [1.6%] had abnormal LVEF with low normal mean GLS. There were no statistically significant predictors of LV dysfunction in this cohort. CONCLUSION: There was a high prevalence of subclinical myocardial dysfunction in the ex-thalassaemic population reiterating the need for close follow up of these patients. 2D Speckle tracking echocardiography-derived LV global longitudinal strain is an effective tool in detecting subclinical myocardial dysfunction in this cohort.